In vitro schistosomicidal activity of tamoxifen and its effectiveness in a murine model of schistosomiasis at a single dose
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Schistosomiasis is a neglected tropical disease affecting 220 million people worldwide. Praziquantel has proven to be effective against this parasitic disease, though there are increasing concerns regarding tolerance/resistance that calls for new drugs. Repurposing already existing and well-known drugs has been a desirable approach since it reduces time, costs, and ethical concerns. The anti-cancer drug tamoxifen (TAM) has been used worldwide for several decades to treat and prevent breast cancer. Previous reports stated that TAM affects Schistosoma hormonal physiology; however, no controlled schistosomicidal in vivo assays have been conducted. In this work, we evaluated the effect of TAM on female and male Schistosoma mansoni morphology, motility, and egg production. We further assessed worm survival and egg production in S. mansoni-infected mice. TAM induced morphological alterations in male and female parasites, as well as in eggs in vitro. Furthermore, in our in vivo experiments, one single dose of intraperitoneal TAM citrate reduced the total worm burden by 73% and led to a decrease in the amount of eggs in feces and low percentages of immature eggs in the small intestine wall. Eggs obtained from TAM citrate-treated mice were reduced in size and presented hyper-vacuolated structures. Our results suggest that TAM may be repurposed as a therapeutic alternative against S. mansoni infections.
KeywordsDrug repurposing Egg Experimental treatment Schistosoma mansoni Tamoxifen
We thank the research funding agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the postgraduate scholarships granted to R.N.O., S.A.P.C., K.M.V., and T.M.
Designed the study: R.N.O., S.M.A., and D.C.M.; performed the experiments: R.N.O., S.A.P.C., K.M.V., and D.C.M; analyzed the data: R.N.O., T.M., S.M.A., and D.C.M.; wrote the paper: T.M., S.M.A., and D.C.M.
FAPESP funds research conducted in S.M.A. and D.C.M.’s laboratory at UNICAMP (process nos. 16/07137-0 and 14/21129-4).
Compliance with ethical standards
The Ethics Commission approved all experiments using rodents (CEUA/UNICAMP, protocol no. 2170-1).
Conflict of interest
The authors declare that they have no conflict of interest.
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